The overall objective of this grant has been the development of new approaches to the surgical treatment of melanoma and other solid neoplasms, utilizing a multidisciplinary approach of pathologic, immunologic and molecular techniques to achieve a more precise "ultra- staging" for melanoma and solid neoplasms, utilizing a multidisciplinary approach of pathologic, immunologic and molecular techniques to achieve a more precise "ultra-staging" for melanoma and solid neoplasms. We are hopeful that the use of these multidisciplinary techniques will reduce the extent of surgery and post-operative adjuvant therapy by differentiating those patients who are curable by surgery alone from those who have residual occult metastases and need post-operative adjuvant therapy. The advent of effect post-surgical adjuvant therapy for AJCC Stages III and IIA/B melanoma in the form of high dose intron-A and intermediate dose Roferon has increased the urgency of achieving this aim. The toxicity and expense of such therapy make it essential to avoid these adjuvant therapies in those patients who are unlikely to recur. The primary Aim of this proposal is to determine whether the innovate technique of lymphatic mapping and sentinel node biopsy, with selective lymphadenectomy, conveys a survival benefit for patients with clinical stage I melanoma with Breslow Thickness greater than 1.0 mm. This technique accurately identifies patients with early stage melanoma who have nodal metastases and are likely to benefit from radical lymphadenectomy. Furthermore, it avoids unnecessary lymph node dissection in those patients whose melanoma failed to metastasize to regional nodes. This new approach has been extended to a multi-center trial, the Multi- center Selective Lymphadenectomy Trial (MSLT), comparing wide excision alone or combined with selective lymphadenectomy. This multi-center trial, which involves 16 melanoma centers, must accrue 800 more patients to answer this important question. Secondary Aims include: (a) development of new pathologic methods to more accurately identify micrometastases in the sentinel node and predict prognosis for individual patients; (b) development of new molecular, immunological and genetic markers to more accurately measure the presence of subclinical micrometastases in the blood and sentinel nodes which provide more precise "ultra-staging" of occult melanoma metastases. The above techniques are applied retrospectively to archival specimens collected in the JWCI and prospectively to patients in the MSLT.